DR3, also known as TRAMP, LARD, WSL-1, or TNFRSF25, is a death-domain containing tumor necrosis receptor that is the closest homolog to TNF-receptor 1, which is a key transducer of inflammatory responses in the innate immune system. DR3 however, is primarily expressed in T cells. TL1A, the TNF-family ligand for DR3, can costimulate T cells, but the physiological function of TL1A-DR3 interactions in immune responses is not known. In studies published this year, we have shown that DR3 is the critical receptor responsible for TL1A-induced T cell costimulation and dendritic cells as the likely source for TL1A during T cell priming. Despite its role in costimulation, DR3 is not required for T cell polarization into Th1, Th2 or Th17 effector subtypes or after priming with model antigens or Toxoplasma gondii. However, DR3 is required on T cells for immunopathology, local T cell accumulation and cytokine production in autoimmune and allergic disease models that depend on diverse effector T cell subsets. DR3 is required for efficient T-cell infiltration and immunopathology in inflamed tissues and may be a promising therapeutic target for autoimmune diseases in which T-cells play a pathogenic role such as Rheumatoid Arthritis, Systemic Lupus Erythematosus, Type-1 diabetes, autoimmune thyroid disease, and others. We are developing novel reagents and mouse models to further investigate the role of TL1A-DR3 interactions in normal and pathological T cell responses.